Vitamin E is a collective name for a family of eight related fat-soluble compounds commonly found in vegetation and seeds with distinctive antioxidant activities, namely the four isomers of tocopherols and four isomers of tocotrienols. The tocopherol and tocotrienol subfamilies are each composed of alpha, beta, gamma and delta that have varying levels of biological activity. Research studies indicate that antioxidants protect cells from the damaging effects of free radicals, which are molecules containing an unpaired electron, and are known to contribute to the development of cancer and cardiovascular disease.
Therefore, vitamin E emerged as an essential fat-soluble nutrient that functions as an antioxidant in the human body to prevent disease and to promote health. Previously, the alpha-tocopherol has been considered to be the most active form. However, recent years of scientific research clearly show that tocotrienols are different from the commonly used vitamin E form i.e. alpha-tocopherol and confer properties that are stronger and often unique from tocopherols. Tocotrienols are distributed throughout the human body via the bloodstream, with particular accumulations found in various body tissues including the brain, heart, skin, cardiac muscle, liver, and adipose tissue after oral dosing. Therefore, recent developments suggest that the tocotrienol subfamily of natural vitamin E is better antioxidant than tocopherol subfamily as having powerful neuroprotective, tumor suppressive effect and cholesterol lowering properties.
The human body absorbs fat and oil in the gastrointestinal system by solubilising them into micelles through the secretion of bile salts and acids, followed by digestion by lipases. There is high inter-individual variability in this absorption process resulting in varying doses between different persons. In addition, the secretion of bile salts and acids is dependent and stimulated by a fatty diet, which can vary greatly between the different meals consumed. Like all fat-soluble nutrients and dietary lipids, the oral absorption of tocotrienols is low, highly variable and dependent upon formulation parameters. To circumvent such variables and to achieve consistent high amount of absorption of fat-based vitamins and drugs including vitamin E tocotrienols, a self-emulsifying drug delivery system (SEDDS) has been developed using different types of surfactants and oil carriers. Existing SEDDS invention for palm-derived vitamin E rich in tocotrienols is able to deliver predominantly the alpha-tocopherol isomer of Vitamin E. Moreover, this delivery is at the expense of tocotrienols isomers, whose antioxidant activity might reach from 40 to 60 times that of tocopherols.
Therefore the need exists for providing a self-emulsifying delivery system with effective formulation that preferentially increases the oral bioavailability of tocotrienol isomers over alpha-tocopherol.
The self-emulsifying formulation of the present invention provides a useful dosage form with consistent and enhanced levels of tocotrienol isomers being absorbed in-vivo upon oral ingestion which is independent of dietary fats.